Sheep uterine gland knockout (UGKO) model.

Area of Science:

• Reproductive Biology
• Developmental Biology
• Epigenetics

Background:

• Endometrial gland development in sheep is a critical postnatal process.
• Epigenetic inhibition by synthetic progestin exposure in ewe lambs disrupts this development.
• This leads to a specific uterine gland knockout (UGKO) phenotype.

Purpose of the Study:

• To establish and characterize the UGKO ewe as a model for studying uterine function.
• To investigate the role of endometrial glands in estrous cyclicity and pregnancy.
• To identify molecular mechanisms underlying pregnancy defects in UGKO ewes.

Main Methods:

• Neonatal exposure of ewe lambs to a synthetic progestin.
• Phenotypic characterization of the UGKO ewe reproductive tract.
• Analysis of estrous cycle alterations and pregnancy outcomes.
• Genomic and proteomic approaches to identify key factors.

Main Results:

• UGKO ewes lack endometrial glands but show normal development of other reproductive structures and the HPO axis.
• UGKO ewes exhibit altered estrous cycles due to impaired prostaglandin F2alpha production.
• Blastocyst survival and elongation are compromised in UGKO ewes, leading to infertility.

Conclusions:

• The UGKO ewe is a valid model for studying endometrial gland function and uterine receptivity.
• Absence of endometrial glands and their secretions is the primary cause of pregnancy failure in UGKO ewes.
• Further research using genomics and proteomics will identify critical histotroph components and markers of uterine function.